The micro-mechanics of single molecules studied with atomic force microscopy

Thomas E. Fisher, Piotr E. Marszalek, Andres F. Oberhauser, Mariano Carrion-Vazquez, Julio M. Fernandez

Research output: Contribution to journalReview articlepeer-review

71 Scopus citations


The atomic force microscope (AFM) in its force-measuring mode is capable of effecting displacements on an angstrom scale (10 Å = 1 nm) and measuring forces of a few piconewtons. Recent experiments have applied AFM techniques to study the mechanical properties of single biological polymers. These properties contribute to the function of many proteins exposed to mechanical strain, including components of the extracellular matrix (ECM). The force-bearing proteins of the ECM typically contain multiple tandem repeats of independently folded domains, a common feature of proteins with structural and mechanical roles. Polysaccharide moieties of adhesion glycoproteins such as the selectins are also subject to strain. Force-induced extension of both types of molecules with the AFM results in conformational changes that could contribute to their mechanical function. The force-extension curve for amylose exhibits a transition in elasticity caused by the conversion of its glucopyranose rings from the chair to the boat conformation. Extension of multi-domain proteins causes sequential unraveling of domains, resulting in a force-extension curve displaying a saw tooth pattern of peaks. The engineering of multimeric proteins consisting of repeats of identical domains has allowed detailed analysis of the mechanical properties of single protein domains. Repetitive extension and relaxation has enabled direct measurement of rates of domain unfolding and refolding. The combination of site-directed mutagenesis with AFM can be used to elucidate the amino acid sequences that determine mechanical stability. The AFM thus offers a novel way to explore the mechanical functions of proteins and will be a useful tool for studying the micro-mechanics of exocytosis.

Original languageEnglish (US)
Pages (from-to)5-14
Number of pages10
JournalJournal of Physiology
Issue number1
StatePublished - Oct 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Physiology


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